Recent outbreaks of Ebola and Zika virus have revealed the threats posed by emerging infectious diseases (EIDs). Although interventions are urgently needed, research during an outbreak can raise logistical and ethical challenges. Human challenge studies, where researchers deliberately expose healthy volunteers to disease, are powerful tools to prepare for future EID outbreaks and accelerate product development. However, some human challenge studies have been controversial, and systematic ethical analysis is limited. The overall objective of this project is to bring together a diverse group of experts and stakeholders to develop a new, comprehensive, and practical ethical framework for the use of human challenge studies for EIDs. This project has two aims: (1) To determine under what conditions human challenge studies on EIDs can be ethically justified, and (2) to identify additional safeguards to protect and respect participants and communities and foster public trust.